CN104101739B - A kind of magnetic tweezers - Google Patents
A kind of magnetic tweezers Download PDFInfo
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- CN104101739B CN104101739B CN201410375357.8A CN201410375357A CN104101739B CN 104101739 B CN104101739 B CN 104101739B CN 201410375357 A CN201410375357 A CN 201410375357A CN 104101739 B CN104101739 B CN 104101739B
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Abstract
The invention belongs to micro-imaging technique field, disclose a kind of magnetic tweezers, for realizing the motor control of individual molecule；Including: sample cell, it is used for holding unimolecule sample and solution；Wherein, unimolecule sample is placed in solution, and described unimolecule sample one end is connected to bottom the coverslip of described sample cell, and the other end connects magnetic ball；Magnet control unit, is positioned at below sample cell, for realizing the motor control of magnetic ball；Image-generating unit, for recording the reflected light signal of described magnetic ball kinestate to sample cell projection light output；Control unit, is used for receiving and change described reflected light signal, it is achieved the motion measurement of described magnetic ball and analysis.The present invention provides the up-downgoing magnetic tweezer of a kind of vertical direction, it is to avoid the systematic error that gravity causes, and is greatly improved certainty of measurement.
Description
Technical field
The present invention relates to micro-imaging technique field, particularly to a kind of magnetic tweezers.
Background technology
Recent two decades comes, and the research in individual molecule level is explosive growth.People have developed glass successively
The single molecule study technology such as glass micropin, atomic force microscope, optical tweezer are directly handled and detect individual molecule.
Compared with above-mentioned several Single Molecule Manipulation Technology, magnetic tweezer has higher dynamometry precision, and will not be to sample
Product cause damage.
In current existing magnetic tweezer technology, when magnetic ball stress is in motion, the most only magnetic force in horizontal direction,
Also being affected by self gravitation, therefore in the vertical direction has the interference of a gravity, and magnetic ball is led
The molecule drawn is in direction obliquely.Now, the motion of bead is not the most the damped pendulum motion of rule.Molecule
Physical length also than horizontal direction measure length longer.And these 2 are calculating bead stress and motion shape
Not being considered into the when of condition, the experimental result precision therefore recorded is the highest.Additionally, it is existing
Magnetic tweezer sample cell is more complicated, make take time, relatively costly；Sample cell Middle molecule distance external magnets is remote,
The magnetic force caused and can apply is less, generally less than 30pN.Owing to the dynamometry principle of tradition magnetic tweezer limits,
The molecule that the following length of micron is shorter can not be measured.
Summary of the invention
The technical problem to be solved is to provide one and evades gravity impact, improving measurement accuracy
Magnetic tweezers.
For solving above-mentioned technical problem, the invention provides a kind of magnetic tweezers, for realizing single point
The motor control of subsample；Including:
Sample cell, is used for holding described unimolecule sample and solution；Wherein, described unimolecule sample is put
In solution, described unimolecule sample one end is connected to bottom the coverslip of described sample cell, the other end
Connect magnetic ball；
Magnet control unit, is positioned at below sample cell, for the motor control of magnetic ball；
Image-generating unit, for recording the reflection of described magnetic ball kinestate to sample cell projection light output
Optical signal；
Control unit, is used for receiving and change described reflected light signal, and the motion carrying out described magnetic ball is surveyed
Amount and analysis.
Further, described magnet control unit includes: permanent magnet, is positioned at below sample cell, passes through
The motion of Magnetic Control magnetic ball；
Electric rotating machine, is fixed on below described permanent magnet, drives described permanent magnet to rotate in horizontal plane；
Linear electric machine, is connected bottom described electric rotating machine, drives described electric rotating machine and permanent magnet
In the vertical direction moves.
Further, described image-generating unit includes: T-shaped pipe, be positioned at T-shaped pipe T-shaped convergence part
Spectroscope, light source and object lens；The optical signal of described light source output is entered by the T-shaped pipe stage casing mouth of pipe,
Through described spectroscope effect, by the object lens being connected with described T-shaped pipe bottom nozzle, project described sample
In product pond；The reflected light signal of the sample cell object lens from the bottom of described T-shaped pipe enter, through T-shaped pipe
Top ports output.
Further, described control unit includes:
Video camera, for collecting the described reflected light signal of the top ports output through T-shaped pipe, and by it
It is converted into the signal of telecommunication；
Controller, is analyzed above-said current signal processing, and obtains kinestate and the stress feelings of magnetic ball
Condition；
Piezoelectric ceramics, is connected with described controller by a voltage amplifier VA, controls described pressure
The deformation of electroceramics and then generation displacement；Wherein, piezoelectric ceramics is connected with the base of described object lens, logical
Cross the displacement of piezoelectric ceramics, drive object lens to move, the diverse location in observing samples pond.
Further, described sample cell includes: microscope slide, cell body, coverslip and liquid storage cylinder；Institute
State microscope slide, cell body and coverslip and stack formation sample cell closed structure；Described liquid storage cylinder passes through hair
Tubule carries solution and sample in sample cell closed structure；Described sample cell closed structure passes through pipeline
Communicate with the external world, discharge solution.
Further, described magnetic tweezers also includes: temperature controller；Described temperature controller is positioned at sample
Chi Shang, is used for controlling temperature in pond.
Further, the precision of described temperature controller is 0.1 DEG C.
Further, described control unit uses dynamometry formula: F=kBT(X+R)/<δy2>, wherein,
kBFor Boltzmann constant, T is thermodynamic temperature, and X is molecular length, and R is magnetic bulb diameter, <
δy2> it is the mean square deviation in magnetic ball Brownian movement y direction.
The magnetic tweezers that the present invention provides, by changing the control mode that structure designs and changes magnetic ball,
Solving in existing magnetic tweezer, gravity affects the systematic error that molecule is measured；That is, by being located at vertically
Magnet control unit on direction coordinates sample cell, and the magnetic ball completing up-downgoing controls, weight the most now
Force direction is identical with magnetic force direction, gravity now is constant, and calculating formula can compensate for, it is to avoid make
Become irregular damped pendulum, and the length of molecule is measured accurately in vertical direction, thus improve measurement
Precision；In addition by optical imagery structure, the kinestate of reflected light signal record magnetic ball, the most necessarily
Optimizing signals collecting flow process in degree, in hgher efficiency, numerical is more preferable, it is simple to analytical calculation.
Accompanying drawing explanation
The structural representation of the magnetic tweezers that Fig. 1 provides for the embodiment of the present invention；
The structural representation of the sample cell that Fig. 2 provides for the embodiment of the present invention；
The sample attachment structure schematic diagram that Fig. 3 provides for the embodiment of the present invention；
The magnetic ball stress schematic diagram that Fig. 4 provides for the embodiment of the present invention.
Detailed description of the invention
Seeing Fig. 1 and Fig. 3, the embodiment of the present invention provides a kind of magnetic tweezers, is used for realizing individual molecule
Motor control；Including:
Sample cell, is used for holding unimolecule sample and solution；Wherein, unimolecule sample is placed in solution,
Unimolecule sample one end is connected to bottom the coverslip of sample cell, and the other end connects magnetic ball；
Magnet control unit, is positioned at below sample cell, for the motor control of magnetic ball；
Image-generating unit, for recording the reflection of described magnetic ball kinestate to sample cell projection light output
Optical signal；
Control unit, is used for receiving and change described reflected light signal, and the motion carrying out described magnetic ball is surveyed
Amount and analysis.
When measuring, drive magnet control unit action by control unit, and then pass through magnetic force
Effect, image-generating unit projects sample cell by light path converting, and collects the reflection light letter reflected and return
Number, it is sent to control unit, through conversion process, calculates stress and the kinestate of magnetic ball.
Magnet control unit includes: permanent magnet 3, is positioned at below sample cell, by Magnetic Control magnetic ball
Motion；
Electric rotating machine 2, is fixed on below permanent magnet 3, drives permanent magnet 3 to rotate in horizontal plane；
Linear electric machine 1, is connected bottom electric rotating machine 2, and motor 2 and permanent magnet 3 are rotated
In the vertical direction moves.
Seeing Fig. 4, the motion of magnetic ball is controlled by permanent magnet 3；At vertical direction by linear electric machine 1
Action, thus regulate the position of permanent magnet 3, and then regulation acts on the magnetic force size and Orientation of magnetic ball；
On the other hand by electric rotating machine 2, adjust the magnetic force direction in horizontal plane, make magnetic ball at horizontal plane
Interior motion, applies moment.
Image-generating unit includes: T-shaped pipe 7, be positioned at T-shaped pipe 7 T-shaped convergence part spectroscope 6,
Light source 10 and object lens；The optical signal of light source 10 output is entered by the T-shaped pipe 7 stage casing mouth of pipe, warp
Spectroscope 6 acts on, and is projected in sample cell by the object lens being connected with T-shaped pipe 7 bottom nozzle；Sample
The reflected light signal in the pond object lens from the bottom of T-shaped pipe 7 enter, through the top ports output of T-shaped pipe 7.
Complete the kinestate collection in sample cell, with the form record of optical signal.
Meanwhile, light path relative closure, image is clear.The transmission of optical signal and collecting efficiency are high, turn
The numerical changed is more preferable.
Cost consumptive material is lower relative to business-like optical microscope.
Control unit includes:
Video camera, for collecting the reflected light signal of the top ports output through T-shaped pipe 7, and by its turn
Change the signal of telecommunication into；
Controller 8, is analyzed above-said current signal processing, and obtains kinestate and the stress of magnetic ball
Situation；
Piezoelectric ceramics 6, is connected with controller by a voltage amplifier VA, controls piezoelectric ceramics 6
Deformation so that produce displacement；Wherein, piezoelectric ceramics 6 is connected with the base of object lens, is made pottery by piezoelectricity
The displacement of porcelain 6, drives object lens to move, the diverse location in observing samples pond.Wherein, permanent magnet is adopted
With opposite polarity two pieces of magnets, the axis about electric rotating machine 2 is symmetrical arranged, thus is formed steady
Fixed magnetic force output.
Advantage of this embodiment is that the impact overcoming gravity to experimental result.In this device, magnetic ball
Outstanding in the vertical direction, magnetic force and gravity direction overlap, and F is the power that molecule is subject to joint efforts, can be by magnetic
The Brownian movement of ball calculates.
Magnetic ball does damped pendulum motion, deviates equilbrium position δ y, restoring force dF during bead warm-up movementy≈-
F δ y/<X>=-kyδy.X is that the length i.e. magnetic ball of DNA is to the distance at sample cell top.Typically recognize
For when X is bigger, approximately more than 200 nanometers, k=F/<X>it is the effective rigidity of this damped pendulum.According to
Energy equipartition theorem, bead is k at the energy of vertical magnetic field direction one degree of freedomBT/2,kBFor Bohr
The most graceful constant, T is thermodynamic temperature, and the energy in the direction is equal to k < δ y2>/2,<δy2> it is
The mean square deviation in magnetic ball Brownian movement y direction.So kBT/2=k < δ y2>/2=F<δ y2>/(2<X>),
Obtain F=kBT<X>/<δy2>.Auto-correlation algorithm program based on fast Fourier transform is utilized to analyze
The video gathered, just obtains the movement locus of magnetic ball.So, δ y and<X>can be divided by image
Analysis directly obtains, then tries to achieve external force size by above formula.Due to energy equipartition theorem, formula
F=kBT<X>/<δy2In>,<δ y2>change<δ z into2>or<δ y2+δz2> be also suitable.
See Fig. 4, when molecular length X≤200 nanometer, for the magnetic ball of diameter 2.8 microns, press
Above-mentioned formula, the maximum, force that magnetic ball is subject to is only about 1pN, and precision is relatively low.The present embodiment carries
The device of confession, Magnet polarized, magnetic bead is suppressed along the warm-up movement of magnetic direction z, y and z side
To warm-up movement the most identical, therefore take y durection component.The present embodiment considers that the extension that magnetic spherical zone comes is long
Degree, dynamometry F=kBT(X+R)/<δy2>, wherein, R is magnetic bulb diameter.Owing to R is some microns,
So F just can be sufficiently large, so this magnetic tweezer can measure the little molecule being as short as 5 nanometers.
Seeing Fig. 2, sample cell includes: microscope slide 9, cell body 10, coverslip 11 and liquid storage cylinder 13；
Microscope slide 9, cell body 10 and coverslip stack formation sample cell closed structure；Liquid storage cylinder 13 passes through
Capillary tube carries solution and sample in sample cell closed structure；Sample cell closed structure passes through pipeline 12
Communicate with the external world, discharge solution.
Magnetic tweezers also includes: temperature controller；Temperature controller is positioned on sample cell, is used for controlling in pond
Temperature, makes that sample solution is more stable, test condition is more accurate.The precision of temperature controller is
0.1℃。
In the present embodiment, the molecule with magnetic ball is put in sample cell solution by glass tubing, in molecule
The one end not connecing magnetic ball adheres on the cover slip.Magnet below sample cell passes through attracting magnetic ball to molecule
Produce the pulling force on a vertical direction, do straight line and rotary motion by magnetic tweezer controller drive magnet,
The size and Orientation of the power suffered by molecule with magnetic ball changes the most therewith.Magnetic ball move through external shooting
Machine imaging is sent to computer PC main frame in real time or controls on computer, and video recording preserves and analyzes.Magnetic ball
The piezoelectric ceramics that is forced through be sent on controller through voltage amplifier VA, gather corresponding data also
Analyze.Dynamometry algorithm introduces magnetic bulb diameter, F=kBT(X+R)/<δy2>, it is possible to measure 5 nanometers to tens
The little molecule that micron is long, range and precision are greatly improved.
The magnetic tweezers that the present invention provides, by changing the control mode that structure designs and changes magnetic ball,
Solving in existing magnetic tweezer, gravity affects the systematic error that molecule is measured；That is, by being located at vertically
Magnet control unit on direction coordinates sample cell, and the magnetic ball completing up-downgoing controls, weight the most now
Force direction is identical with magnetic force direction, gravity now is steady state value, and calculating formula can compensate for, it is to avoid make
Become irregular damped pendulum, thus improve certainty of measurement；In addition by optical imagery structure, light is reflected
The kinestate of signal record magnetic ball, optimizes signals collecting flow process the most to a certain extent, in hgher efficiency,
Numerical is more preferable, it is simple to analytical calculation.
It should be noted last that, above detailed description of the invention is only in order to illustrate technical scheme
And unrestricted, although the present invention being described in detail with reference to example, the ordinary skill people of this area
Member should be appreciated that and can modify technical scheme or equivalent, without deviating from
The spirit and scope of technical solution of the present invention, it all should be contained in the middle of scope of the presently claimed invention.
Claims (8)
1. a magnetic tweezers, for realizing the motor control to unimolecule sample；It is characterized in that,
Including:
Sample cell, is used for holding described unimolecule sample and solution；Wherein, described unimolecule sample is put
In solution, described unimolecule sample one end is connected to bottom the coverslip of described sample cell, the other end
Connect magnetic ball；
Magnet control unit, is positioned at below sample cell, for the motor control of magnetic ball；
Image-generating unit, for recording the reflection of described magnetic ball kinestate to sample cell projection light output
Optical signal；
Control unit, is used for receiving and change described reflected light signal, and the motion carrying out described magnetic ball is surveyed
Amount and analysis；
Wherein, the magnet control unit below sample cell produces one vertically by attracting magnetic ball to molecule
Pulling force on direction, does straight line and rotary motion, the power suffered by magnetic ball by magnetic tweezer controller drive magnet
Size and Orientation change the most therewith.
2. magnetic tweezers as claimed in claim 1, it is characterised in that described magnet control unit bag
Include: permanent magnet, be positioned at below sample cell, by the motion of Magnetic Control magnetic ball；
Electric rotating machine, is fixed on below described permanent magnet, drives described permanent magnet to rotate in horizontal plane；
Linear electric machine, is connected bottom described electric rotating machine, drives described electric rotating machine and permanent magnet
In the vertical direction moves.
3. magnetic tweezers as claimed in claim 1, it is characterised in that described image-generating unit includes:
T-shaped pipe, it is positioned at spectroscope, light source and the object lens of T-shaped pipe T-shaped convergence part；Described light source is defeated
The optical signal gone out is entered by the T-shaped pipe stage casing mouth of pipe, acts through and described T-shaped through described spectroscope
The object lens that pipe bottom nozzle is connected project in described sample cell；The reflected light signal of sample cell is from described T
The object lens of the bottom of shape pipe enter, through the top ports output of T-shaped pipe.
4. magnetic tweezers as claimed in claim 3, it is characterised in that described control unit includes:
Video camera, for collecting the described reflected light signal of the top ports output through T-shaped pipe, and by institute
State reflected light signal and be converted into the signal of telecommunication；
Controller, is analyzed above-said current signal processing, and obtains kinestate and the stress feelings of magnetic ball
Condition；
Piezoelectric ceramics, is connected with described controller by a voltage amplifier VA, controls described pressure
The deformation of electroceramics and then generation displacement；Wherein, piezoelectric ceramics is connected with the base of described object lens, logical
Cross the displacement of piezoelectric ceramics, drive object lens to move, the diverse location in observing samples pond.
5. magnetic tweezers as claimed in claim 1, it is characterised in that described sample cell includes: carry
Slide, cell body, coverslip and liquid storage cylinder；Described microscope slide, cell body and coverslip stack formation
Sample cell closed structure；Described liquid storage cylinder by capillary tube carry in sample cell closed structure solution and
Sample；Described sample cell closed structure is communicated with the external world by pipeline, discharges solution.
6. magnetic tweezers as claimed in claim 5, it is characterised in that also include: temperature controller；
Described temperature controller is positioned on sample cell, is used for controlling temperature in pond.
7. magnetic tweezers as claimed in claim 6, it is characterised in that: the precision of described temperature controller
It it is 0.1 DEG C.
8. magnetic tweezers as claimed in claim 1, it is characterised in that: described control unit uses to be surveyed
Power formula: F=kBT(X+R)/<δy2>, wherein, kBFor Boltzmann constant, T is thermodynamic temperature,
X is molecular length, and R is magnetic bulb diameter, < δ y2> it is the mean square deviation in magnetic ball Brownian movement y direction.
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104374697B (en) * | 2014-11-10 | 2017-02-15 | 华中科技大学 | Magnetic tweezers and optical tweezers measuring and controlling system |
| CN105004702A (en) * | 2015-06-18 | 2015-10-28 | 华中科技大学 | Dual-imaging magnetic tweezer system |
| CN110360925B (en) * | 2018-04-10 | 2020-10-27 | 中国科学院物理研究所 | Calibration method and calibration device for magnetic sphere coordinates of magnetic tweezers device |
| CN108645795B (en) * | 2018-04-28 | 2020-01-14 | 华南理工大学 | Multi-channel single-protein magnetic tweezers measurement and control method and system |
| CN110320186B (en) * | 2019-06-06 | 2021-03-30 | 华南理工大学 | Multi-channel flow cavity and magnetic tweezers composite detection system and method |
| CN111965142B (en) * | 2020-07-03 | 2022-03-29 | 华南理工大学 | Sub-nanometer optical detection system and detection method thereof |
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| CN1869650A (en) * | 2006-05-29 | 2006-11-29 | 中国科学院物理研究所 | Monomolecular control transverse magnetic forceps device |
| CN203203917U (en) * | 2013-04-10 | 2013-09-18 | 温州大学 | Magnetic tweezers device capable of controlling temperature |
| CN103424386A (en) * | 2012-05-24 | 2013-12-04 | 中国科学院物理研究所 | Single molecule fluorescence apparatus and application method thereof |
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| NL2004928C2 (en) * | 2010-06-21 | 2011-12-22 | Univ Delft Tech | Method for determining one or more characterizing features of a macromolecule and an apparatus for carrying out said method. |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1869650A (en) * | 2006-05-29 | 2006-11-29 | 中国科学院物理研究所 | Monomolecular control transverse magnetic forceps device |
| CN103424386A (en) * | 2012-05-24 | 2013-12-04 | 中国科学院物理研究所 | Single molecule fluorescence apparatus and application method thereof |
| CN203203917U (en) * | 2013-04-10 | 2013-09-18 | 温州大学 | Magnetic tweezers device capable of controlling temperature |
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